User:Novafields/Alternating electric field therapy

From Wikipedia, the free encyclopedia

Article Draft[edit]

Lead[edit]

Alternating electric field therapy, sometimes called tumor treating fields (TTFields), is a type of electromagnetic field therapy using low-intensity, intermediate frequency electrical fields to treat cancer.[1][2][3][4] TTFields disrupt cell division by disrupting dipole alignment and inducing dielectrophoresis of critical molecules and organelles during mitosis. The use of TTFields is approved in the United States and Europe for the treatment of newly diagnosed and recurrent glioblastoma multiforme (GBM), and is undergoing clinical trials for several other tumor types.[5]

something about Novocure?

TTField-generating device manufactured by the Israeli company Novocure Despite earning regulatory approval, the efficacy of this technology remains controversial among medical experts.[2][6]

Article body[edit]

Mechanism

All living cells contain polar molecules and will respond to changes in electric fields.[7] Alternating electric field therapy, or Tumor Treating Fields (TTFields) use insulated electrodes to apply very-low-intensity, intermediate-frequency alternating electrical fields to a target area containing cancerous cells.[8][7] Polar molecules play a key role in cell division, making mitosis particularly susceptible to interference from outside electric fields. TTFields disrupt dipole alignment and induce dielectrophoresis during mitosis, killing proliferating cells.[9][8][10][11][12][13]

Dipole Alignment

Septin movement inhibited by TTFields

Polar molecules critical to mitosis include α/β-tubulin and the septin heterotrimer.[12] Tubulin is necessary for mitotic spindle formation during metaphase, while septins stabilize the cell during cytokinesis. When exposed to TTFields, these molecules align their dipole with the electric field, freezing them in one orientation. This prevents tubulin and septin molecules from moving to and binding where they are needed for successful cell division.[14] This results in mitotic catastrophe, initiating cell death through apoptosis.[14] Uneven chromosome splitting can also be a result of TTFields' affect on dipole alignment, resulting in daughter cells with abnormal chromosome numbers.[7][15]

TTFields induce dielectrophoresis in dividing cells

Dielectrophoresis

Cells that successfully complete metaphase are later susceptible to TTFields during telophase.[7] At this stage in cell division, the cell takes on an hourglass shape as it prepares to divide in two. This results in a non-uniform electric field within the cell, with high field density at the cell's furrow. This causes polar molecules and organelles to migrate with the electric field toward the furrow.[15][13][7] This disrupts the cell's division and leads to cell death.

In principle, this approach could be selective for cancer cells in regions of the body, such as the brain, where the majority of normal cells are non-proliferating.[9] The frequency of the TTField can be adjusted between 100 and 300kHz to target cancer cells and avoid harming healthy cells.[15][10] Current research supports that cell size is inversely proportional to optimal TTField frequency.[7][13] TTFields can also be optimized by orienting two transducer arrays perpendicular to each other to maximize the amount of cells that will be affected. Cells divide in different orientations and are most affected by an electric field that is parallel to their direction of division (perpendicular to the mitotic plate).[15][13][7] Clinicians determine where to place the transducer arrays to optimize treatment using software that analyzes tumor location and the patient's morphometry.[13] Emerging evidence suggests that alternating electric field therapy disrupts various biological processes,[16] including DNA repair,[17][18] cell permeability[19] and immunological responses,[20] to elicit therapeutic effects. Greater mechanistic understanding of TTFields may pave the way for new, more effective TTFields-based therapeutic combinations in the future.[21]

Medical Uses

Recurrent Glioblastoma

Newly Diagnosed Glioblastoma

Recurrent Ovarian Carcinoma

Medical Device

Side Effects

Regulatory Approval

Company

References[edit]

  1. ^ Rominiyi, Ola; Vanderlinden, Aurelie; Clenton, Susan Jane; Bridgewater, Caroline; Al-Tamimi, Yahia; Collis, Spencer James (2020-11-04). "Tumour treating fields therapy for glioblastoma: current advances and future directions". British Journal of Cancer. 124 (4): 697–709. doi:10.1038/s41416-020-01136-5. ISSN 1532-1827. PMC 7884384. PMID 33144698.
  2. ^ a b "NCCN Guidelines for CNS cancers" (PDF). Retrieved 4 August 2013.
  3. ^ Kirkpatrick, John (October 2014). "Recurrent Malignant Gliomas". Seminars in Radiation Oncology. 24 (4): 289–298. doi:10.1016/j.semradonc.2014.06.006. PMC 4522935. PMID 25219814.
  4. ^ Johnson, Derek (August 2014). "Medical Management of High-Grade Astrocytoma: Current and Emerging Therapies". Seminars in Oncology. 41 (4): 511–522. doi:10.1053/j.seminoncol.2014.06.010. PMID 25173143.
  5. ^ "ClinicalTrials.gov results-Novocure". ClinicalTrials.gov. Retrieved 26 December 2014.
  6. ^ Wick, Wolfgang (25 February 2016). "TTFields: where does all the skepticism come from?". Neuro-Oncology. 18 (3): 303–305. doi:10.1093/neuonc/now012. PMC 4767251. PMID 26917587.
  7. ^ a b c d e f g Hottinger, Andreas F.; Pacheco, Patricia; Stupp, Roger (2016-10). "Tumor treating fields: a novel treatment modality and its use in brain tumors". Neuro-Oncology. 18 (10): 1338–1349. doi:10.1093/neuonc/now182. ISSN 1523-5866. PMC 5035531. PMID 27664860. {{cite journal}}: Check date values in: |date= (help)
  8. ^ a b Kirson, Eilon D.; Gurvich, Zoya; Schneiderman, Rosa; Dekel, Erez; Itzhaki, Aviran; Wasserman, Yoram; Schatzberger, Rachel; Palti, Yoram (1 May 2004). "Disruption of Cancer Cell Replication by Alternating Electric Fields". Cancer Research. 64 (9): 3288–3295. doi:10.1158/0008-5472.CAN-04-0083. PMID 15126372.
  9. ^ a b Calzón Fernández S, Llanos Méndez A (2013). Tumor treating fields therapy (TTFields) for glioblastoma. A systematic review of the literature (PDF) (Systematic review) (in Spanish). Agencia de Evaluación de Tecnologías Sanitarias de Andalucía. ISBN 978-84-15600-12-1.
  10. ^ a b Kirson ED, Dbalý V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y (12 June 2007). "Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors". PNAS. 104 (24): 10152–7. Bibcode:2007PNAS..10410152K. doi:10.1073/pnas.0702916104. PMC 1886002. PMID 17551011.
  11. ^ Mrugala, Maciej M. (25 April 2013). "Advances and Challenges in the Treatment of Glioblastoma: A Clinician's Perspective". Discovery Medicine. 15 (83): 221–230. PMID 23636139.
  12. ^ a b Swanson, K; et al. (2016). "An Overview of Alternating Electric Fields Therapy (NovoTTF Therapy) for the Treatment of Malignant Glioma". Current Neurology and Neuroscience Reports. 16 (1): 8. doi:10.1007/s11910-015-0606-5. PMC 4703612. PMID 26739692.
  13. ^ a b c d e Mun, Elijah J.; Babiker, Hani M.; Weinberg, Uri; Kirson, Eilon D.; Von Hoff, Daniel D. (2018-01-15). "Tumor-Treating Fields: A Fourth Modality in Cancer Treatment". Clinical Cancer Research. 24 (2): 266–275. doi:10.1158/1078-0432.CCR-17-1117. ISSN 1078-0432.
  14. ^ a b Gera, Nidhi; Yang, Aaron; Holtzman, Talia S.; Lee, Sze Xian; Wong, Eric T.; Swanson, Kenneth D. (2015-05-26). Prigent, Claude (ed.). "Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit". PLOS ONE. 10 (5): e0125269. doi:10.1371/journal.pone.0125269. ISSN 1932-6203. PMC 4444126. PMID 26010837.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  15. ^ a b c d "TUMOR TREATING FIELDS". XVIVO Scientific Animation. Retrieved 2023-11-21.
  16. ^ Rominiyi, Ola; Vanderlinden, Aurelie; Clenton, Susan Jane; Bridgewater, Caroline; Al-Tamimi, Yahia; Collis, Spencer James (2020-11-04). "Tumour treating fields therapy for glioblastoma: current advances and future directions". British Journal of Cancer. 124 (4): 697–709. doi:10.1038/s41416-020-01136-5. ISSN 1532-1827. PMC 7884384. PMID 33144698.
  17. ^ Giladi, Moshe; Munster, Mijal; Schneiderman, Rosa S.; Voloshin, Tali; Porat, Yaara; Blat, Roni; Zielinska-Chomej, Katarzyna; Hååg, Petra; Bomzon, Ze'ev; Kirson, Eilon D.; Weinberg, Uri (2017-12-29). "Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells". Radiation Oncology. 12 (1): 206. doi:10.1186/s13014-017-0941-6. ISSN 1748-717X. PMC 5747183. PMID 29284495.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  18. ^ Karanam, Narasimha Kumar; Ding, Lianghao; Aroumougame, Asaithamby; Story, Michael D. (March 2020). "Tumor treating fields cause replication stress and interfere with DNA replication fork maintenance: Implications for cancer therapy". Translational Research: The Journal of Laboratory and Clinical Medicine. 217: 33–46. doi:10.1016/j.trsl.2019.10.003. ISSN 1878-1810. PMID 31707040.
  19. ^ Chang, Edwin; Patel, Chirag B.; Pohling, Christoph; Young, Caroline; Song, Jonathan; Flores, Thomas Anthony; Zeng, Yitian; Joubert, Lydia-Marie; Arami, Hamed; Natarajan, Arutselvan; Sinclair, Robert (2018). "Tumor treating fields increases membrane permeability in glioblastoma cells". Cell Death Discovery. 4: 113. doi:10.1038/s41420-018-0130-x. ISSN 2058-7716. PMC 6281619. PMID 30534421.
  20. ^ Kirson, Eilon D.; Giladi, Moshe; Gurvich, Zoya; Itzhaki, Aviran; Mordechovich, Daniel; Schneiderman, Rosa S.; Wasserman, Yoram; Ryffel, Bernhard; Goldsher, Dorit; Palti, Yoram (2009). "Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs". Clinical & Experimental Metastasis. 26 (7): 633–640. doi:10.1007/s10585-009-9262-y. ISSN 1573-7276. PMC 2776150. PMID 19387848.
  21. ^ Rominiyi, Ola; Vanderlinden, Aurelie; Clenton, Susan Jane; Bridgewater, Caroline; Al-Tamimi, Yahia; Collis, Spencer James (2020-11-04). "Tumour treating fields therapy for glioblastoma: current advances and future directions". British Journal of Cancer. 124 (4): 697–709. doi:10.1038/s41416-020-01136-5. ISSN 1532-1827. PMC 7884384. PMID 33144698.
Retrieved from "https://en.wikipedia.org/w/index.php?title=User:Novafields/Alternating_electric_field_therapy&oldid=1188526617"